Maternal haemoglobin concentrations before and during pregnancy and stillbirth risk: A population-based case-control study

Background: Results of previous studies on the association between maternal haemoglobin concentration during pregnancy and stillbirth risk are inconclusive. It is not clear if haemoglobin concentration before pregnancy has a role. Using prospectively collected information from pre-pregnancy and antenatal visits, we investigated associations of maternal haemoglobin concentrations before and during pregnancy and haemoglobin dilution with stillbirth risk. Methods: In a population-based case-control study from rural Golestan, a province in northern Iran, we identified 495 stillbirths (cases) and randomly selected 2,888 control live births among antenatal health-care visits between 2007 and 2009. Using logistic regression, we estimated associations of maternal haemoglobin concentrations, haemoglobin dilution at different stages of pregnancy, with stillbirth risk. Results: Compared with normal maternal haemoglobin concentration (110-120g/l) at the end of the second trimester, high maternal haemoglobin concentration (≥140g/l) was associated with a more than two-fold increased stillbirth risk (OR = 2.31, 95% CI [1.30-4.10]), while low maternal haemoglobin concentration (<110g/l) was associated with a 37% reduction in stillbirth risk. Haemoglobin concentration before pregnancy was not associated with stillbirth risk. Decreased haemoglobin concentration, as measured during pregnancy (OR = 0.61, 95% CI [0.46, 0.80]), or only during the second trimester (OR = 0.75, 95% CI [0.62, 0.90]), were associated with reduced stillbirth risk. The associations were essentially similar for preterm and term stillbirths. Conclusions: Haemoglobin concentration before pregnancy is not associated with stillbirth risk. High haemoglobin level and absence of haemoglobin dilution during pregnancy could be considered as indicators of a high-risk pregnancy. © 2016 The Author(s)

Maternal smoking during pregnancy, other prenatal and perinatal factors, and the risk of Legg-Calvé-Perthes disease

OBJECTIVE. The causes of Legg-Calvé-Perthes disease are largely unknown, but this pediatric disease seems to result from interruption of the blood supply to the proximal femur and is considered a vascular disease. Because maternal smoking during pregnancy influences fetal development and is associated with cardiovascular diseases in offspring, we hypothesized that this exposure is a risk for Legg-Calvé- Perthes disease and also investigated other markers of impaired fetal development and early-life exposures. MATERIALS AND METHODS. The Swedish Inpatient Register identified 852 individuals with a diagnosis of Legg-Calvé-Perthes disease from 1983 to 2005, individually matched by year of birth, age, sex, and region of residence with 4432 randomly selected control subjects. Linkage with the Swedish Medical Birth Register provided information on prenatal factors, including maternal smoking. Conditional logistic regression examined associations of maternal smoking during pregnancy and the other measures with the risk of Legg-Calvé-Perthes disease in offspring, adjusted for socioeconomic index and other potential confounding factors. RESULTS. Maternal smoking during pregnancy was associated with an increased Legg-Calvé-Perthes disease risk, and heavy smoking was associated with a risk increase of almost 100%. Very low birth weight and cesarean section were independently associated with ̃240% and 36% increases in the risk of Legg-Calvé-Perthes disease, respectively. CONCLUSION. Maternal smoking during pregnancy and other factors indicated by impaired fetal development may be associated with an increased risk of Legg-Calvé- Perthes disease

Risk of diabetes and cardiovascular disease in patients with primary sclerosing cholangitis

Background & Aims Primary sclerosing cholangitis (PSC) is associated with increased mortality. Cardiovascular disease is a leading cause of death in the Western world. We examined the risk of cardiovascular disease and diabetes (type 1 and type 2) in patients with PSC and their first-degree relatives. Methods This prospective multicentre cohort study included 678 individuals with PSC diagnosed between 1970 and 2004, and 6347 non-PSC reference individuals matched for age, and sex. Through linkage of the Swedish Multigeneration Register we identified 3139 first-degree relatives to PSC patients and 30,953 first-degree relatives to the matched comparison cohort. We retrieved data on cardiovascular disease and type 1 and type 2 diabetes (T1D and T2D) from the National Patient Register, and then examined the association with PSC or having a family history of PSC using Poisson regression. Results During 125,127 person-years of follow-up, 203 individuals with PSC had a diagnosis of cardiovascular disease. This corresponded to a 3.34-fold increased relative risk (RR) of cardiovascular disease in individuals with PSC (95% CI = 2.86-3.91). The highest risk estimates were seen for diseases of the arteries, veins, and lymphatic vessels while the RR was neutral for ischemic heart disease (0.90) or only slightly elevated for cerebrovascular disease (1.74). Meanwhile, PSC first-degree relatives were at no increased risk of cardiovascular disease (RR = 0.87; 95% CI = 0.80-0.95). Individuals with PSC (RR = 7.95; 95% CI = 4.82-13.12), and to some extent also their first-degree relatives (RR = 1.73; 95% CI = 1.19-2.52) were at increased risk of T1D. Also for T2D were the RR is higher in individuals with PSC (RR = 2.54; 95% CI = 1.56-4.13) than in PSC first-degree relatives (RR = 0.81; 95% CI = 0.65-1.02). Conclusions PSC was associated with T1D, T2D, and non-ischemic cardiovascular disease. In contrast, first-degree relatives to PSC patients were only at a moderately increased risk of T1D, and at no increased risk of either cardiovascular disease or T2D. © 2013 European Association for the Study of the Liver. Published

Consanguineous marriage, prepregnancy maternal characteristics and stillbirth risk: A population-based case-control study

Introduction. Consanguineous marriage is associated with increased risks for congenital anomalies, low birthweight, and other adverse perinatal outcomes. In this population-based, case-control study we investigated the association between consanguineous marriage (first-cousin marriage) and stillbirth risk, using prospectively collected information from prepregnancy visits. Material and methods. From 2007 to 2009, we identified 283 stillbirths (cases) and 2088 randomly selected live control births through prepregnancy visits in rural Golestan, Iran. The associations between consanguinity and prepregnancy maternal characteristics and stillbirth risk were examined using multivariate logistic regression. Results. The rate of consanguineous marriage was 19.4% among cases and 13.6% among controls. Consanguinity was associated with increased stillbirth risk [odds ratio (OR) 1.53; 95% CI 1.10-2.14]. The association was significantly increased for preterm stillbirth (< 37 gestational weeks) (OR 2.43; 95% CI 1.46-4.04) but not for term stillbirth (≥ 37 weeks) (OR 1.14; 95% CI 0.75-1.74). Low and high maternal age, underweight, obesity, nulliparity, a history of infertility or miscarriage, previous obstetric complications (preeclampsia, preterm delivery, and stillbirth in previous pregnancies) were also associated with increased stillbirth risks. Conclusions. Consanguineous marriage is associated with increased risk of stillbirth, particularly preterm stillbirth. Findings for other maternal risk factors for stillbirth in rural Iran are consistent with previously reported findings from high-income countries. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology

Appendicectomy and multiple sclerosis risk

Background: Appendicectomy for acute appendicitis, but not for other causes, is inversely associated with immune-mediated diseases such as ulcerative colitis, suggesting appendicitis is a marker of immune characteristics influencing immune-mediated disease risk. This study investigated the association of appendectomy and its underlying diagnosis with multiple sclerosis (MS). Methods: Swedish general population registers and the Swedish MS register provided information on 20542 cases with MS diagnosed between 1964-2006 and 204157 controls matched for age, sex, period and region. Appendicectomy prior to MS diagnosis was identified in 673 cases and 6518 controls. Conditional logistic regression, with adjustment for socio-economic index, assessed the association of diagnosis underlying appendicitis with MS risk. Results: A perforated appendix, the best indicator of acute appendicitis in this material, was inversely associated with MS, although not statistically significantly, with an odds ratio (and 95% confidence interval of 0.86 (0.70-1.04). The odds ratios are 1.04 (0.94-1.16) for appendicitis without perforation and 1.14 (0.98-1.33) for appendectomy without appendicitis. Conclusion: Although inconclusive in terms of assessing the hypothesis, these results may help to explain why earlier studies of appendicitis and MS risk have been inconsistent, as there may be variation in association by diagnosis underlying appendicectomy. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS

Cancer risk among patients with cystic fibrosis and their first-degree relatives

Patients with cystic fibrosis (CF) are at increased risk of some cancers. Little is known about the cancer risks among carriers heterozygous for the CF mutation and it is hypothesized this may be associated with reduced cancer risk. Using Swedish general population-based registers, we identified 884 patients with CF from 1968 to 2003 and 3,033 of their first-degree relatives The subjects were followed from birth of index persons or 1958, whichever came later, until death, emigration or 2003, whichever came first. Cancer risks were compared with the general Swedish population using standardized incidence ratios (SIR) with 95% confidence intervals (CI). Patients, followed for an average of 21 years, were at a higher overall risk of cancer. Some 26 cancer diagnoses, after excluding multiple diagnoses of nonmelanoma skin cancer in one man, produced an overall SIR of 3.2 (95%CI 2.1-4.6).We found statistically significantly increased risks for kidney, thyroid, endocrine, lymphoma and nonmelanoma skin cancer. There was no modification of cancer risk among parents and siblings, with an average of 21 years of follow-up. This study did not identify a heterozygote advantage for CF gene mutations in relation to cancer risk. © 2009 UICC

Cancer risk among patients with multiple sclerosis and their parents

Background: We investigated cancer risk among patients with multiple sclerosis (MS) and whether variation by age at MS diagnosis helps to elucidate mechanisms underlying the previously reported reduced cancer risk. We also studied cancer risk among parents to ascertain if MS susceptibility genes may confer protection against cancer in relatives. Methods: Cox proportional hazards regression, adjusted for age, sex, area, and socioeconomic index, estimated cancer risk among 20,276 patients with MS and 203,951 individuals without MS, using Swedish general population register data. Similar analyses were conducted among 11,284 fathers and 12,006 mothers of patients with MS, compared with 123,158 fathers and 129,409 mothers of controls. Results: With an average of 35 years of follow-up, there was a decreased overall cancer risk among patients with MS (hazard ratio = 0.91, 0.87-0.95). Increased risks were observed for brain tumors (1.44, 1.21-1.72) and urinary organ cancer (1.27, 1.05-1.53). Parents of patients with MS did not have a notably increased or decreased overall cancer risk. Conclusions: The reduction in cancer risk in patients with multiple sclerosis (MS) may result from behavioral change, treatment, or we speculate that some immunologic characteristics of MS disease activity improve antitumor surveillance. The lack of association among parents indicatesthat a simple inherited characteristic is unlikely to explain the reduced cancer risk among patients with MS. MS is associated with increased risk for some cancers, such as of urinary organs and brain tumors (although surveillance bias may be responsible). copyright © by AAN Enterprises, Inc

Cystic fibrosis gene mutations and gastrointestinal diseases

Background: This study examined if CF mutation heterozygosity is associated with diseases of gastrointestinal epithelial barrier function. Design and methods: Swedish registers identified 865 patients with a diagnosis of CF between 1968 and 2003 and matched with 8101 individuals without CF. Gastrointestinal disease risk was examined among 1534 biological parents and 1396 siblings of CF patients, compared with 15,526 parents and 15,542 siblings of individuals without CF. Results: First-degree relatives of CF patients were not at lower risk of the gastrointestinal diseases, in contrast with a raised risk among CF patients. Conclusion: Heterozygosity for CF gene mutations does not protect against gastrointestinal diseases where impaired barrier function may be relevant. © 2010 European Cystic Fibrosis Society

A Population-Based Study of the Risk of Diabetic Retinopathy in Patients With Type 1 Diabetes and Celiac Disease

Objective: Celiac disease (CD) is associated with type 1 diabetes (T1D). In the current study, we examined whether CD affects the risk of diabetic retinopathy (DRP) in patients with T1D. Research design and methods: This was a population-based cohort study. Through the Swedish National Patient Register, we identified 41,566 patients diagnosed with diabetes in 1964–2009 and who were ≤30 years of age at diagnosis. CD was defined as having villous atrophy (Marsh stage 3) according to small intestinal biopsies performed between 1969 and 2008, with biopsy reports obtained from Sweden’s 28 pathology departments. During follow-up, 947 T1D patients had a diagnosis of CD. We used Cox regression analysis with CD as a time-dependent covariate to estimate adjusted hazard ratios (aHRs) for DRP in patients with T1D and CD and compared them with patients with T1D but no CD. Results: Duration of CD correlated with the risk of DRP. When results were stratified by time since CD diagnosis, individuals with T1D and CD were at a lower risk of DRP in the first 5 years after CD diagnosis (aHR 0.57 [95% CI 0.36–0.91]), followed by a neutral risk in years 5 to <10 (1.03 [0.68–1.57]). With longer follow-up, coexisting CD was a risk factor for DRP (10 to <15 years of follow-up, aHR 2.83 [95% CI 1.95–4.11]; ≥15 years of follow-up, 3.01 [1.43–6.32]). Conclusions: Having a diagnosis of CD for >10 years is a risk factor for the development of DRP in T1D. Long-standing CD in patients with T1D merits intense monitoring of DRP

Antipyretic, parasitologic, and immunologic effects of combining sulfadoxine/pyrimethamine with chloroquine or paracetamol for treating uncomplicated Plasmodium falciparum malaria

Sulfadoxine/pyrimethamine (SP) is increasingly used against malaria in sub-Saharan Africa because of chloroquine resistance. However, chloroquine may have a beneficial antipyretic effect. We therefore compared the combination of SP plus chloroquine, chloroquine alone, SP alone, and SP plus paracetamol in the treatment of uncomplicated Plasmodium falciparum malaria in 175 Tanzanian children (1-4 years old) in a randomized trial. Outcome variables were axillary temperatures every six hours, daily parasitemias, and serum levels of IgG antibodies to P. falciparum. Lower mean temperatures (6-48 hours) were achieved with SP plus chloroquine or paracetamol than with SP alone (P \u3c 0.001) or chloroquine alone (P \u3c 0.05). All three SP-treated groups showed high and similar parasite reduction (0-48 hours), whereas treatment with chloroquine alone was much less effective. Levels of IgG antibodies to P. falciparum increased significantly (P \u3c 0.001) and similarly in the four treatment groups between days 0, 2. and 3. Thus, the addition of chloroquine or paracetamol to SP improved the clinical outcome, but did not affect the parasitologic response or antibody production